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Endometrial hyperplasia (view source)

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:''See [[Endometrium]] for dating and benign pathologies.''
:''See [[Endometrium]] for an introduction to the topic.''
'''Endometrial hyperplasia''', abbreviated '''EH''', is a precursor to [[endometrial carcinoma]].
'''Endometrial hyperplasia''', abbreviated '''EH''', is a precursor to [[endometrial carcinoma]].


=Overview=
=Overview=
The most widely used system is from the World Health Organization (WHO).  
===WHO endometrial hyperplasia classification of 2014===
The 2014 WHO system has two categories:<ref name=pmid25797956 >{{Cite journal  | last1 = Emons | first1 = G. | last2 = Beckmann | first2 = MW. | last3 = Schmidt | first3 = D. | last4 = Mallmann | first4 = P. | title = New WHO Classification of Endometrial Hyperplasias. | journal = Geburtshilfe Frauenheilkd | volume = 75 | issue = 2 | pages = 135-136 | month = Feb | year = 2015 | doi = 10.1055/s-0034-1396256 | PMID = 25797956 }}</ref>
*Hyperplasia without atypia.
*Atypical hyperplasia/endometrioid intraepithelial neoplasia.


===WHO classification - overview===
===WHO endometrial hyperplasia classification of 1994===
The WHO system is based on determining:
The 1994 WHO system is based on determining:<ref name=pmid25797956>{{Cite journal  | last1 = Emons | first1 = G. | last2 = Beckmann | first2 = MW. | last3 = Schmidt | first3 = D. | last4 = Mallmann | first4 = P. | title = New WHO Classification of Endometrial Hyperplasias. | journal = Geburtshilfe Frauenheilkd | volume = 75 | issue = 2 | pages = 135-136 | month = Feb | year = 2015 | doi = 10.1055/s-0034-1396256 | PMID = 25797956 }}</ref>
# Gland density (normal = ''simple hyperplasia'', high density = ''complex hyperplasia'').
# Gland density (normal/low = ''simple hyperplasia'', high density = ''complex hyperplasia'').
# Presence/absence of nuclear atypia.  
# Presence/absence of nuclear atypia.  
It consists of four categories:
*[[Simple endometrial hyperplasia]].
*[[Simple endometrial hyperplasia with atypia]].
*[[Complex endometrial hyperplasia]].
*[[Complex endometrial hyperplasia with atypia]].


===Alternate classifications - overview===
===Alternate classifications - overview===
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#Endometrial intraepithelial neoplasia (EIN).
#Endometrial intraepithelial neoplasia (EIN).


==WHO classification==
==WHO classification of 1994==
===Management of endometrial hyperplasia===
===Management of endometrial hyperplasia===
*Endometrial hyperplasia with atypia is usually treated with hysterectomy.<ref>URL: [http://www.aafp.org/afp/990600ap/3069.html http://www.aafp.org/afp/990600ap/3069.html].</ref>
*Endometrial hyperplasia with atypia is usually treated with hysterectomy.<ref>URL: [http://www.aafp.org/afp/990600ap/3069.html http://www.aafp.org/afp/990600ap/3069.html].</ref>
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**Progestins + close follow-up ''OR'' hysterectomy.
**Progestins + close follow-up ''OR'' hysterectomy.


===Risk of progression to carcinoma===
===Risk of progression to carcinoma as per 1994 system===
Approximate risk of progression to [[endometrial carcinoma]] - Latta rule of 3s:<ref>Latta, E. January 2009.</ref>
Approximate risk of progression to [[endometrial carcinoma]] - Latta rule of 3s:<ref>Latta, E. January 2009.</ref>
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=WHO system=
==WHO system of 1994 - detail articles==
Almost all hyperplasia is seen in the context of proliferative-type endometrium. [[Endometrial hyperplasia with secretory changes|Hyperplasia in the secretory-type endometrium]] is extremely rare and something diagnosed by or in consultation with an expert in gynecologic pathology.
Almost all hyperplasia is seen in the context of proliferative-type endometrium. [[Endometrial hyperplasia with secretory changes|Hyperplasia in the secretory-type endometrium]] is extremely rare and something diagnosed by or in consultation with an expert in gynecologic pathology.


==Simple endometrial hyperplasia==
===Simple endometrial hyperplasia===
*[[AKA]] ''simple hyperplasia''.
*[[AKA]] ''simple hyperplasia''.
===General===
{{Main|Simple endometrial hyperplasia}}
*More common than simple endometrial hyperplasia with atypia.
*Very low risk for progressing to [[endometrioid endometrial carcinoma]].
 
===Microscopic===
Features:<ref name=Ref_GP236>{{Ref GP|236}}</ref>
*Irregular dilated glands (with large lumens) - '''key feature'''.
**Glands described as "animal shapes".
*Variation of gland size.
*No nuclear atypia.
**Uniform columnar nuclei.
*Normal gland density (gland area in plane of section/total area ~= 1/3).
 
DDx:
*[[Disordered proliferative phase]].
*[[Complex endometrial hyperplasia]] - has increased gland-to-stroma ratio.
*[[Atrophic endometrium|Cystic atrophy of the endometrium]] - does not have proliferative activity.<ref name=pmid16873562>{{Cite journal  | last1 = McCluggage | first1 = WG. | title = My approach to the interpretation of endometrial biopsies and curettings. | journal = J Clin Pathol | volume = 59 | issue = 8 | pages = 801-12 | month = Aug | year = 2006 | doi = 10.1136/jcp.2005.029702 | PMID = 16873562 | PMC = 1860448 }}</ref>
*[[Benign endometrial polyp]] - has thick-walled blood vessels; simple endometrial hyperplasia should not be diagnosed in a polyp.<ref name=pmid16873562/>
 
Images:
*[http://commons.wikimedia.org/wiki/File:Simple_endometrial_hyperplasia_-_low_mag.jpg Simple endometrial hyperplasia - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Simple_endometrial_hyperplasia_-_high_mag.jpg Simple endometrial hyperplasia - high mag. (WC)].
 
==Simple endometrial hyperplasia with atypia==
===General===
*Very uncommon.
 
===Microscopic===
Features:<ref name=Ref_GP236>{{Ref GP|236}}</ref>
*Irregular dilated glands (with large lumens) - '''important feature'''.
**Glands described as "animal shapes".
*Variation of gland size.
*No nuclear atypia.
**Uniform columnar nuclei.
*Normal gland density (gland area in plane of section/total area ~= 1/3).
*Nuclear atypia:<ref>{{Cite journal  | last1 = Silverberg | first1 = SG. | title = Problems in the differential diagnosis of endometrial hyperplasia and carcinoma. | journal = Mod Pathol | volume = 13 | issue = 3 | pages = 309-27 | month = Mar | year = 2000 | doi = 10.1038/modpathol.3880053 | PMID = 10757341 }}</ref>
**Loss of basal nuclear stratification.
**Nuclear size variation.
**Nuclear rounding.
***Nuclei lacking atypical = uniform columnar nuclei.
**Nucleoli.
**Hyperchromasia or vesicular nuclei.
 
Notes:
*There are no clear criteria for atypia. Different sources list different features.
*VL criteria for atypia (all should be present):
*#Increased NC ratio.
*#*Atypical: ~ 1:2
*#*Not atypical: ~1:3.
*#Oval nuclei with small major axis to minor axis ratio.
*#*Atypical: major axis:minor axis = <=2:1.
*#*Not atypical: major axis:minor axis = >=3:1
*#**NB: round nuclei: major axis:minor axis = 1:1.
*#Small nucleoli (~1/5 the size of the nucleus).


==Complex endometrial hyperplasia==
===Simple endometrial hyperplasia with atypia===
{{Main|Simple endometrial hyperplasia}}


===Microscopic===
===Complex endometrial hyperplasia===
Features:
*Abbreviated ''CEH''.
*Increase in size & number of glands + irregular shape - '''key feature'''.
{{Main|Complex endometrial hyperplasia}}
*Cell stratification.
*Nuclear enlargement.
*Mitoses common.
*No nuclear atypia.


Notes:
===Complex endometrial hyperplasia with atypia===
*Normal "gland-to-stroma ratio" is 1:3.
*Two "touching" glands may be one gland in section.
 
DDx:
*[[Complex endometrial hyperplasia with atypia]].
*[[Endometrioid endometrial carcinoma]] - see ''[[endometrial carcinoma versus complex endometrial hyperplasia]]''.
 
Image:
*[http://www.webpathology.com/image.asp?n=1&Case=568 Endometrial hyperplasia (webpathology.com)].
 
====Endometrial carcinoma versus complex endometrial hyperplasia====
Complex endometrial hyperplasia:
*Non-confluent - glands distinct from one another.
 
=====Classic criteria for endometrial carcinoma=====
This is pimping material that shows up on exams.
 
Endometrial carcinoma has one of the following:<ref name=Ref_GP239>{{Ref GP|239}}</ref><ref name=pmid7074572>{{Cite journal  | last1 = Kurman | first1 = RJ. | last2 = Norris | first2 = HJ. | title = Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well-differentiated carcinoma. | journal = Cancer | volume = 49 | issue = 12 | pages = 2547-59 | month = Jun | year = 1982 | doi =  | PMID = 7074572 }}</ref><ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Endometrium_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Endometrium_11protocol.pdf]. Accessed on: 12 January 2012.</ref>
#Desmoplastic stromal response.
#Confluent cribriform growth. †
#Extensive papillary growth. †
#Severe cytologic atypia. †
 
Note:
* † There is a size cut-off for criteria 2, 3 and 4: > 2.1 mm.<ref name=pmid7074572/>
How to remember '''ABCDE''':
*'''A'''typia '''B'''ad.
*'''C'''onfluent cribriform growth.
*'''D'''esmoplasia.
*'''E'''xtensive papillary growth.
 
==Complex endometrial hyperplasia with atypia==
*[[AKA]] ''complex atypical hyperplasia''.
*[[AKA]] ''complex atypical hyperplasia''.
===General===
{{Main|Complex endometrial hyperplasia}}
*High risk of transformation to [[endometrial carcinoma]].
 
===Microscopic===
Features:
*Increase in size & number of glands + irregular shape - '''key feature'''.
*Cell stratification.
*Nuclear enlargement.
*Nuclear atypia:
**Round nuclei ~ 2-3x the size of a lymphocyte.
**Grey/translucent chromatin.
**Nucleoli.
*Mitoses common.
 
Note:
*Atypical nuclei often hide between non-typical nuclei, like peg cells in the [[fallopian tube]].
 
DDx:
*[[Complex endometrial hyperplasia]].
*[[Endometrioid endometrial carcinoma]] - see ''[[endometrial carcinoma versus complex endometrial hyperplasia]]''.
 
Image:
*[http://www.webpathology.com/image.asp?n=2&Case=568 Complex endometrial hyperplasia with atypia (webpathology.com)].
 
===Sign out===
====Insufficient confluence for carcinoma====
<pre>
ENDOMETRIUM, BIOPSY:
- COMPLEX ENDOMETRIAL HYPERPLASIA WITH ATYPIA, SEE COMMENT.
 
COMMENT:
The sections show architecturally complex crowded glands with focal
morular squamous metaplasia and focal cribriforming.  Desmoplasia
is not identified. The degree of gland confluence is not considered
sufficient for the diagnosis of endometrial carcinoma. Nuclear atypia
is present focally.
</pre>
 
====Insufficient extent for carcinoma====
<pre>
ENDOMETRIUM, BIOPSY:
- COMPLEX ENDOMETRIAL HYPERPLASIA WITH ATYPIA, SEE COMMENT.
 
COMMENT:
The sections show architecturally complex back-to-back glands with focal
morular squamous metaplasia and cribriforming. Desmoplasia is not present.
The extent, i.e. the size of the abnormality, is not considered sufficient
for the diagnosis of endometrial carcinoma.
</pre>


=Other=
=Other=
Michael
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